Diallyl Disulfide Attenuates IL-1β/NF-κB-Induced Impairment of Osteogenic Differentiation in Bone Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) play a pivotal role in skeletal regeneration. However, their osteogenic potential can be compromised under inflammatory conditions through interleukin-1β (IL-1β)-mediated activation of nuclear factor kappa B (NF-κB) signaling pathway. This study investigated the protective effects of diallyl disulfide (DADS) against IL-1β/NF-κB-induced impairment of osteogenic differentiation in BMSCs and explored the underlying mechanisms. Human BMSCs were characterized by morphology, tri-lineage differentiation capacity, and surface marker expression. Cells were treated with IL-1β with or without DADS. Assays were conducted to evaluate cell viability, osteogenic gene expression, matrix mineralization, oxidative stress markers, and the expression levels of proteins involved in the NF-κB and AMP-activated protein kinase (AMPK) signaling pathways. The role of AMPK was further examined by co-treatment with the AMPK inhibitor Compound C. IL-1β suppressed osteogenic differentiation and induced oxidative stress in a concentration-dependent manner via activation of the NF-κB signaling pathway. DADS reversed these effects by restoring the expression levels of osteogenic markers (RUNX2, OSX, and OCN), enhancing matrix mineralization, reducing reactive oxygen species (ROS) and malondialdehyde MDA levels, increasing glutathione peroxidase (GSH-PX) activity, and promoting AMPK phosphorylation. The protective effects of DADS were abolished by AMPK inhibition, indicating that its regulatory action is AMPK-dependent. These findings suggest that DADS could alleviate IL-1β-induced osteogenic dysfunction in BMSCs by modulating redox homeostasis and inhibiting NF-κB signaling through AMPK activation. These findings highlighted the therapeutic potential of DADS for inflammation-related bone diseases.